Submissions for variant NM_153240.5(NPHP3):c.2881C>G (p.Gln961Glu)

gnomAD frequency: 0.00036  dbSNP: rs144989330

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001094790	SCV000441094	uncertain significance	Nephronophthisis 3	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000338978	SCV000441095	uncertain significance	Renal-hepatic-pancreatic dysplasia 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000403658	SCV000441096	uncertain significance	NPHP3-related Meckel-like syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000283901	SCV000552114	uncertain significance	Nephronophthisis	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 961 of the NPHP3 protein (p.Gln961Glu). This variant is present in population databases (rs144989330, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical features of nephronophthisis-associated ciliopathy (PMID: 23188109). ClinVar contains an entry for this variant (Variation ID: 343382). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV000727224	SCV000582804	uncertain significance	not provided	2020-06-29	criteria provided, single submitter	clinical testing	Reported as heterozygous in a patient with nephronophthisis associated ciliopathy; no additional information was provided (Halbritter et al., 2012); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23188109)
Eurofins Ntd Llc (ga)	RCV000727224	SCV000706741	uncertain significance	not provided	2017-10-25	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764465	SCV000895530	uncertain significance	Renal-hepatic-pancreatic dysplasia 1; Nephronophthisis 3; NPHP3-related Meckel-like syndrome	2022-05-05	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000727224	SCV001923805	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000727224	SCV001927763	likely benign	not provided		no assertion criteria provided	clinical testing